基于响应面法、BP神经网络结合GA的蛇床子素纳米混悬剂制备工艺优化及体外评价OA

Objective:To prepare osthole nanosuspension(OST-NS)and evaluate its drug release in vitro.Methods:OST-NS was prepared via the miniaturized media milling method.With average particle size and polydispersity coefficient(PDI)as the evaluation indexes,the preparation process of OST-NS was optimized by Box-Behnken response surface method,back propagation(BP)neural network combined with genetic algorithm(GA),and the lyophilized OST-NS powder was prepared.OST-NS was characterized by transmission electron microscopy(TEM),differential scanning calorimetry(DSC),X-ray diffraction(XRD),and Fourier transform infrared spectroscopy(FT-IR),and its in vitro release was evaluated via the dialysis bag method.Results:The preparation conditions of OST-NS were as follows:osthole dosage of 60 mg,saponin dosage of 50.39 mg,zirconia bead volume of 4.3 mL,grinding speed of 1 200 r·min-1(centrifugal radius of 1.5 cm),and grinding time of 2.9 h.The OST-NS prepared with the optimal process showed the average particle size of 237.1 nm,PDI of 0.219,and Zeta potential of-34.4 mV.The in vitro release results showed that the cumulative release of OST-NS after 24 h was(92.68±0.69)%,which conformed to the First-order release model.The appearance of OST-NS was spherical.DSC and FT-IR results indicated that osthole was dispersed in the nanosuspension in an amorphous state or completely encapsulated by the stabilizer,which was beneficial for its dissolution.Conclusion:The preparation process of OST-NS is reasonable and feasible,and it can improve the dissolution of OST.